Decreased metastatic phenotype in cells resistant to aminolevulinic acid-photodynamic therapy.

Decreased metastatic phenotype in cells resistant to aminolevulinic acid-photodynamic therapy.
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DOI:
10.1016/j.canlet.2008.06.023
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发表时间:
2008-11-28
期刊:
影响因子:
9.7
通讯作者:
Batlle, Alcira
Batlle, Alcira
中科院分区:
医学1区
文献类型:
--
作者:
Casas, Adriana;Di Venosa, Gabriela;Vanzulli, Silvia;Perotti, Christian;Mamome, Leandro;Rodriguez, Lorena;Simian, Marina;Juarranz, Angeles;Pontiggia, Osvaldo;Hasan, Tayyaba;Batlle, Alcira

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光动力疗法(PDT)是一种利用光敏剂、可见光和氧气治疗癌症的新型疗法。光动力疗法通常会留下大量存活的肿瘤细胞。在以前的工作中,我们分离并研究了两个来自乳腺癌LM3系(Int.J·奥科尔。29(2006)397-405)。克隆4和克隆8表现出更多的成纤维细胞和树突,并且比亲本更大。在本工作中,我们研究了两个克隆的转移潜能,并与LM3进行了比较。我们发现LM3细胞100%侵袭Matrigel,而Clon 4和Clon 8细胞仅侵袭19±6%和24±7%。此外,100%的LM3细胞向趋化刺激迁移,而克隆4和克隆8分别有38±8%和73±10%的细胞能够迁移。在体内,注射LM3的小鼠100%发生自发性肺转移,而Clon8没有发生自发性肺转移,只有一只注射Clon4的小鼠发生了自发性肺转移。不同细胞间的蛋白水解酶谱无差异。在体内,耐药克隆的锚定依赖性黏附也受到损害,表现为较低的载瘤率、潜伏期和生长率,尽管两个克隆在体外与I型胶原的结合率较高,但没有过表达β1整合素。这是第一个研究细胞对光动力疗法的转移潜能的工作。PDT强烈影响这些细胞的侵袭性表型,可能与更高的胶原结合力有关。这些发现可能对转移性肿瘤的ALA-PDT的结果至关重要,尽管需要进一步的研究来推断使用其他光敏剂和细胞类型的临床结果。
Photodynamic therapy (PDT) is a novel cancer treatment utilising a photosensitiser, visible light and oxygen. PDT often leaves a significant number of surviving tumour cells. In a previous work, we isolated and studied two PDT resistant clones derived from the mammary adenocarcinoma LM3 line (Int. J. Oncol. 29 (2006) 397–405). The isolated Clon 4 and Clon 8 exhibited a more fibroblastic, dendritic pattern and were larger than the parentals. In the present work we studied the metastatic potential of the two clones in comparison with LM3. We found that 100 % of LM3 invaded Matrigel, whereas only 19 ± 6 % and 24 ± 7 % of Clon 4 and Clon 8 cells invaded. In addition, 100% of LM3 cells migrated towards a chemotactic stimulus whereas 38 ± 8 % and 73 ± 10 % of Clones 4 and 8 respectively were able to migrate. In vivo, 100% of the LM3 injected mice developed spontaneous lung metastasis, whereas none of the Clon 8 did, and only one of the mice injected with Clon 4 did. No differences were found in the proteolytic enzyme profiles among the cells. Anchorage-dependent adhesion was also impaired in vivo in the resistant clones, evidenced by the lower tumour take, latency time and growth rates, although both clones showed in vitro higher binding to collagen I without overexpression of β1 integrin. This is the first work where the metastatic potential of cells surviving to PDT has been studied. PDT strongly affects the invasive phenotype of these cells, probably related to a higher binding to collagen. These findings may be crucial for the outcome of ALA-PDT of metastatic tumours, although further studies are needed to extrapolate the results to the clinic employing another photosensitisers and cell types.
DOI: 10.1158/0008-5472.can-06-1793
发表时间: 2006-11-15
期刊: CANCER RESEARCH
影响因子: 11.2
作者:
Kosharskyy, Boleslav;Solban, Nicolas;Hasan, Tayyaba
通讯作者: Hasan, Tayyaba
DOI: 10.1111/j.1751-1097.1986.tb09506.x
发表时间: 1986-02-01
影响因子: 3.3
作者:
DENSTMAN, SC;DILLEHAY, LE;WILLIAMS, JR
通讯作者: WILLIAMS, JR
DOI: 10.1016/1011-1344(90)85083-9
发表时间: 1990-06-01
影响因子: 5.4
作者:
KENNEDY, JC;POTTIER, RH;PROSS, DC
通讯作者: PROSS, DC
DOI: 10.1016/s0016-5085(98)70527-x
发表时间: 1998-03-01
期刊: GASTROENTEROLOGY
影响因子: 29.4
作者:
Gossner, L;Stolte, M;Ell, C
通讯作者: Ell, C
DOI: 10.1016/0020-711x(93)90687-a
发表时间: 1993-10-01
期刊: INTERNATIONAL JOURNAL OF BIOCHEMISTRY
影响因子: --
作者:
FUKUDA, H;CASAS, A;BATLLE, AMC
通讯作者: BATLLE, AMC